Trial Outcomes & Findings for Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Duchenne Muscular Dystrophy (NCT NCT02851797)

Last Updated: 2023-02-02

Results Overview

The time (in seconds) to climb 4 standard-sized stairs is a TFT that represents stair-climbing ability. The test was evaluated by qualified functional evaluators (ie, physiotherapists) who were different from the site personnel who reviewed subjects' safety results. The test was performed in a standardised manner described in a specific site manual. Baseline 4SC was the measurement taken at the randomization assessment, unless this was missing, in which case baseline was taken as the last non missing value recorded prior to or on the date of first study treatment. The shorter the time, the better the outcome.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

179 participants

Primary outcome timeframe

Baseline and 18 months

Results posted on

2023-02-02

Participant Flow

Within the overall population, a total of 118 subjects were enrolled in the givinostat group. A total of 61 subjects were enrolled in the placebo group.

Participant milestones

Participant milestones
Measure	Givinostat Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Overall Study STARTED	118	61
Overall Study All Enrolled Subjects	118	61
Overall Study ITT Population	118	61
Overall Study Safety Set	118	61
Overall Study PK Analysis Set	117	0
Overall Study Target Population	81	39
Overall Study MR Cohort	77	37
Overall Study COMPLETED	111	59
Overall Study NOT COMPLETED	7	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Givinostat Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Overall Study Withdrawal by Subject	4	2
Overall Study Adverse Event	3	0

Baseline Characteristics

Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Duchenne Muscular Dystrophy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Givinostat n=118 Participants Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=61 Participants Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.	Total n=179 Participants Total of all reporting groups
Age, Categorical <=18 years	118 Participants n=5 Participants	61 Participants n=7 Participants	179 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	9.78 years STANDARD_DEVIATION 2.022 • n=5 Participants	9.97 years STANDARD_DEVIATION 2.082 • n=7 Participants	9.84 years STANDARD_DEVIATION 2.039 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	118 Participants n=5 Participants	61 Participants n=7 Participants	179 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	109 Participants n=5 Participants	58 Participants n=7 Participants	167 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	106 Participants n=5 Participants	57 Participants n=7 Participants	163 Participants n=5 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Canada	9 participants n=5 Participants	6 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Netherlands	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Belgium	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants	19 participants n=7 Participants	43 participants n=5 Participants
Region of Enrollment Italy	24 participants n=5 Participants	13 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment United Kingdom	10 participants n=5 Participants	3 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Israel	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment France	9 participants n=5 Participants	5 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Serbia	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Germany	13 participants n=5 Participants	2 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Spain	17 participants n=5 Participants	6 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 18 months

Population: ITT analysis set: the intent-to-treat (ITT) analysis set included all subjects who were randomised, received at least one dose of study drug, and had at least 1 non-missing post-baseline 4SC measure or missing post-baseline 4SC measure due to being either non-ambulatory or otherwise physically unable to perform the assessment, irrespective of any deviation from the protocol or premature discontinuation.

Outcome measures

Outcome measures
Measure	Givinostat n=81 Participants Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=39 Participants Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Mean Change From Baseline in 4 Standard Stairs (4SC) Climb After 18 Months of Treatment	1.27 seconds Standard Error 0.040	1.48 seconds Standard Error 0.058

SECONDARY outcome

Timeframe: Baseline and 18 months

An analysis of time (in seconds) to rise from the floor by change from baseline at 18 months is presented for the Target Population in the ITT analysis set. The shorter the time, the better the outcome.

Outcome measures

Outcome measures
Measure	Givinostat n=81 Participants Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=39 Participants Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Mean Change From Baseline in Time to Rise From Floor After 18 Months of Treatment	9.33 seconds Interval 5.821 to 12.838	12.61 seconds Interval 7.491 to 17.724

SECONDARY outcome

Timeframe: Baseline and 18 months

This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. The 6-Minute Walk Test is a useful measure of functional capacity targeted at people with at least moderately severe impairment. A modified version of the 6MWT recommended by American Thoracic Society (2002) for use in adults was performed. The longer the walked distance the better the outcome.

Outcome measures

Outcome measures
Measure	Givinostat n=81 Participants Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=39 Participants Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Mean Change From Baseline in the Six-minute Walking Test (6MWT) After 18 Months of Treatment	-38.43 meters Interval -50.704 to -26.153	-48.38 meters Interval -66.288 to -30.482

SECONDARY outcome

Timeframe: Baseline and 18 months

The total North Star Ambulatory Assessment (NSAA) is a 17-item rating scale that is used to measure functional motor abilities in ambulant children with Duchenne Muscular Dystrophy (DMD). It is usually used to monitor the progression of the disease and treatment effects. The 17 items of the NSAA, ranging from standing to running 10 meters, were graded using the standard score card with each assessment rated as 0 - unable to achieve independently, 1 - modified method but achieves goal independent of physical assistance from another, or 2 - normal with no obvious modification of activity. This scale is ordinal with 0 as the minimum score (indicating full disfunctionality, i.e. the worst outcome) and with 34 as the maximum score indicating fully-independent function (the best outcome).

Outcome measures

Outcome measures
Measure	Givinostat n=81 Participants Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=39 Participants Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Mean Change From Baseline in Total North Star Ambulatory Assessment (NSAA) Score After 18 Months of Treatment	-2.66 score on a scale Interval -3.563 to -1.759	-4.58 score on a scale Interval -5.891 to -3.26

SECONDARY outcome

Timeframe: over 18 months

Subject cumulative number of failures across all postbaseline visits was the endpoint of interest for analysis. For each subject at each postbaseline visit, failure to perform each of the 17 items of the NSAA was assessed, where "failure" was defined as a score transition from 2 or 1 at baseline to 0 at the respective visit. The total number of failed items for the visit was calculated (maximum of 17 failed items per visit per subject). The subject's cumulative number of failures across all visits was the sum of the total failures at each postbaseline visit.

Outcome measures

Outcome measures
Measure	Givinostat n=81 Participants Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=39 Participants Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Cumulative Loss of Function on the NSAA	3.42 cumulative number of failures Interval 2.692 to 4.334	5.56 cumulative number of failures Interval 4.002 to 7.715

SECONDARY outcome

Timeframe: Baseline and 18 months

The mean change of muscle strength normalized was evaluated by knee extension and elbow flexion normalized by subject weight, both measured by hand-held myometry (HHM).

Outcome measures

Outcome measures
Measure	Givinostat n=81 Participants Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=39 Participants Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Mean Change From Baseline of Muscle Strength Normalized Overtime Overall knee extension	-0.32 Newtons/kg Interval -0.441 to -0.197	-0.50 Newtons/kg Interval -0.681 to -0.328
Mean Change From Baseline of Muscle Strength Normalized Overtime Overall elbow flexion	-0.10 Newtons/kg Interval -0.174 to -0.031	-0.19 Newtons/kg Interval -0.292 to -0.085

SECONDARY outcome

Timeframe: Baseline and 18 months

Population: MR cohort: the MR cohort included all subjects in the Target Population who were randomised to study treatment and completed at least one post-baseline MRI/MRS assessment.

Vastus lateralis muscle fat fraction (VL MFF) was expressed as fat infiltration in this muscle. Fat infiltration was assessed by Magnetic Resonance (MRS).

Outcome measures

Outcome measures
Measure	Givinostat n=77 Participants Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=37 Participants Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Mean Change From Baseline in Vastus Lateralis Muscle Fat Fraction (VL MFF) at 18 Months	7.63 percentage of fat Interval 6.098 to 9.172	10.56 percentage of fat Interval 8.331 to 12.783

SECONDARY outcome

Timeframe: Baseline through end of study, that is the end of 18° month

Population: SAF analysis set: the safety analysis set included all subjects who were randomized and received at least 1 dose of study drug.

Adverse Events are unfavorable changes in health, including abnormal laboratory findings, that occur in trial participants during the clinical trial or within a specified period following the trial. Serious Adverse Events include adverse events that result in death, require either inpatient hospitalization or the prolongation of hospitalization, are life-threatening, result in a persistent or significant disability/incapacity or result in a congenital anomaly/birth defect. Other important medical events, based upon appropriate medical judgment, may also be considered Serious Adverse Events if a trial participant's health is at risk and intervention is required to prevent an outcome mentioned.

Outcome measures

Outcome measures
Measure	Givinostat n=118 Participants Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=61 Participants Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Number of Subjects Experiencing Treatment-emergent AEs (TEAEs), Serious AEs (SAEs), Mild TEAE Moderate TEAE, Severe TEAE Subjects with severe AE	5 Participants	1 Participants
Number of Subjects Experiencing Treatment-emergent AEs (TEAEs), Serious AEs (SAEs), Mild TEAE Moderate TEAE, Severe TEAE Subjects with TEAE	112 Participants	57 Participants
Number of Subjects Experiencing Treatment-emergent AEs (TEAEs), Serious AEs (SAEs), Mild TEAE Moderate TEAE, Severe TEAE Subjects with serious AE	8 Participants	2 Participants
Number of Subjects Experiencing Treatment-emergent AEs (TEAEs), Serious AEs (SAEs), Mild TEAE Moderate TEAE, Severe TEAE Subjects with mild AE	69 Participants	39 Participants
Number of Subjects Experiencing Treatment-emergent AEs (TEAEs), Serious AEs (SAEs), Mild TEAE Moderate TEAE, Severe TEAE Subjects with moderate AE	38 Participants	17 Participants

SECONDARY outcome

Timeframe: Week 4, EOS, early withdrawal

Population: SAF analysis set: the safety analysis set included all subjects who were randomised and received at least 1 dose of study drug.

Acceptability and palatability of the oral suspension over time are presented. More in details, child perception of the medicine at the three timepoints hereunder specified; parent perception of the medicine based on the child's reaction at the same three timepoints; and parent problems administering the medication at the same timepoints are reported.

Outcome measures

Outcome measures
Measure	Givinostat n=118 Participants Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=61 Participants Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - week 4 - dislike very much	31 Participants	11 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent admin - early withdrawal - yes	0 Participants	0 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - week 4 - dislike a little	21 Participants	17 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - week 4 - not sure	30 Participants	16 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - week 4 - like a little	19 Participants	12 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - week 4 - like very much	11 Participants	3 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - EOS - dislike very much	21 Participants	7 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - EOS - dislike a little	24 Participants	13 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - EOS - not sure	34 Participants	16 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - EOS - like a little	19 Participants	10 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - EOS - like very much	7 Participants	9 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - early withdrawal - dislike very much	1 Participants	0 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - early withdrawal - dislike a little	1 Participants	0 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - early withdrawal - not sure	2 Participants	0 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - early withdrawal - like a little	1 Participants	0 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Child perception - early withdrawal - like very much	0 Participants	0 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent perception - week 4 - unpleasant	50 Participants	31 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent perception - week 4 - not sure	28 Participants	10 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent perception - week 4 - pleasant	35 Participants	18 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent perception - EOS - unpleasant	42 Participants	14 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent perception - EOS - not sure	40 Participants	22 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent perception - EOS - pleasant	26 Participants	19 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent perception - early withdrawal - unpleasant	1 Participants	0 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent perception - early withdrawal - not sure	3 Participants	0 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent perception - early withdrawal - pleasant	1 Participants	0 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent admin problems - week 4 - yes	6 Participants	1 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent admin problems - week 4 - no	107 Participants	58 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent admin problems - EOS - yes	5 Participants	0 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent admin problems - EOS - no	102 Participants	55 Participants
Evaluation of Acceptability/Palatability of the Oral Suspension Parent admin - early withdrawal - no	5 Participants	0 Participants

Adverse Events

Givinostat

Serious events: 8 serious events

Other events: 112 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Givinostat n=118 participants at risk Givinostat oral suspension (10 mg/mL) twice daily givinostat: The oral suspension of givinostat (10 mg/mL) was to be dosed in fed condition as described below: Givinostat or placebo starting dose * \> or =10 and \< 12.5 kg of weight: 13.3 mg bid = 1.3 ml oral suspension bid * \> or =12.5 and \< 20 kg: 16.7 mg bid =1.7 ml oral suspension bid * \> or = 20 and \< 25 kg: 20 mg bid = 2.0 ml oral suspension bid * \> or = 25 and \< 30 kg: 23.3 mg bid = 2.3 ml oral suspension bid * \> or = 30 and \< 40 kg: 26.7 mg bid = 2.7 ml oral suspension bid * \> or = 40 and \< 50 kg: 33.3 mg bid = 3.3 ml oral suspension bid * \> or = 50 and \< 60 kg: 36.7 mg bid = 3.7 ml oral suspension bid * \> or = 60 and \< 70 kg: 40 mg bid = 4 ml oral suspension bid * \> or = 70 kg: 46.7 mg bid = 4.7 ml oral suspension bid	Placebo n=61 participants at risk Placebo oral suspension (10 mg/mL) twice daily placebo: the oral suspension of placebo, manufactured to mimic givinostat, was to be dosed in fed condition as described for givinostat.
Infections and infestations Gastroenteritis	0.85% 1/118 • Number of events 1 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).	3.3% 2/61 • Number of events 2 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).
Infections and infestations Gastroenteritis viral	0.85% 1/118 • Number of events 1 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).	0.00% 0/61 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).
Infections and infestations Influenza	0.85% 1/118 • Number of events 1 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).	0.00% 0/61 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).
Gastrointestinal disorders Abdominal pain	0.85% 1/118 • Number of events 1 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).	0.00% 0/61 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).
Gastrointestinal disorders Vomiting	0.85% 1/118 • Number of events 1 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).	0.00% 0/61 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).
General disorders Chest pain	0.85% 1/118 • Number of events 1 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).	0.00% 0/61 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).
Injury, poisoning and procedural complications Spinal fracture	0.85% 1/118 • Number of events 1 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).	0.00% 0/61 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).
Nervous system disorders Dizziness	0.85% 1/118 • Number of events 1 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).	0.00% 0/61 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).
Skin and subcutaneous tissue disorders Rash	0.85% 1/118 • Number of events 1 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).	0.00% 0/61 • Throughout the study till the end of study (month 18, visit 15). More precisely at Visits 4 and 7 (month 1), at Visit 9 (month 2), at Visit 10 (month 3), at Visit 11 (month 6), at Visit 12 (month 9), at Visit 13 (month 12), at Visit 14 (month 15), at Visit 15 (EOS, month 18) and at the FUV (Follow-Up Visit to be performed after 4 weeks from the last dose of study drug (ie, 4 weeks ± 7 days)).

Other adverse events

Additional Information

Dr Paolo Bettica, MD and PhD

Italfarmaco SpA

Phone: +3902 66041503

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place